Cargando…

Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling

In the past decades, hepatocellular carcinoma (HCC) has been receiving increased attention due to rising morbidity and mortality in both developing and developed countries. Koumine, one of the significant alkaloidal constituents of Gelsemium elegans Benth., has been regarded as a promising anti-infl...

Descripción completa

Detalles Bibliográficos
Autores principales: Yuan, Zhihang, Liang, Zengenni, Yi, Jine, Chen, Xiaojun, Li, Rongfang, Wu, Jing, Sun, Zhiliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843837/
https://www.ncbi.nlm.nih.gov/pubmed/31581704
http://dx.doi.org/10.3390/biom9100559
_version_ 1783468309549678592
author Yuan, Zhihang
Liang, Zengenni
Yi, Jine
Chen, Xiaojun
Li, Rongfang
Wu, Jing
Sun, Zhiliang
author_facet Yuan, Zhihang
Liang, Zengenni
Yi, Jine
Chen, Xiaojun
Li, Rongfang
Wu, Jing
Sun, Zhiliang
author_sort Yuan, Zhihang
collection PubMed
description In the past decades, hepatocellular carcinoma (HCC) has been receiving increased attention due to rising morbidity and mortality in both developing and developed countries. Koumine, one of the significant alkaloidal constituents of Gelsemium elegans Benth., has been regarded as a promising anti-inflammation, anxiolytic, and analgesic agent, as well as an anti-tumor agent. In the present study, we attempted to provide a novel mechanism by which koumine suppresses HCC cell proliferation. We demonstrated that koumine might suppress the proliferation of HCC cells and promote apoptosis in HCC cells dose-dependently. Under koumine treatment, the mitochondria membrane potential was significantly decreased while reactive oxygen species (ROS) production was increased in HCC cells; in the meantime, the phosphorylation of ERK, p38, p65, and IκBα could all be inhibited by koumine treatment dose-dependently. More importantly, the effects of koumine upon mitochondria membrane potential, ROS production, and the phosphorylation of ERK, p38, p65, and IκBα could be significantly reversed by ROS inhibitor, indicating that koumine affects HCC cell fate and ERK/p38 MAPK and NF-κB signaling activity through producing excess ROS. In conclusion, koumine could inhibit the proliferation of HCC cells and promote apoptosis in HCC cells; NF-κB and ERK/p38 MAPK pathways could contribute to koumine functions in a ROS-dependent manner.
format Online
Article
Text
id pubmed-6843837
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68438372019-11-25 Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling Yuan, Zhihang Liang, Zengenni Yi, Jine Chen, Xiaojun Li, Rongfang Wu, Jing Sun, Zhiliang Biomolecules Article In the past decades, hepatocellular carcinoma (HCC) has been receiving increased attention due to rising morbidity and mortality in both developing and developed countries. Koumine, one of the significant alkaloidal constituents of Gelsemium elegans Benth., has been regarded as a promising anti-inflammation, anxiolytic, and analgesic agent, as well as an anti-tumor agent. In the present study, we attempted to provide a novel mechanism by which koumine suppresses HCC cell proliferation. We demonstrated that koumine might suppress the proliferation of HCC cells and promote apoptosis in HCC cells dose-dependently. Under koumine treatment, the mitochondria membrane potential was significantly decreased while reactive oxygen species (ROS) production was increased in HCC cells; in the meantime, the phosphorylation of ERK, p38, p65, and IκBα could all be inhibited by koumine treatment dose-dependently. More importantly, the effects of koumine upon mitochondria membrane potential, ROS production, and the phosphorylation of ERK, p38, p65, and IκBα could be significantly reversed by ROS inhibitor, indicating that koumine affects HCC cell fate and ERK/p38 MAPK and NF-κB signaling activity through producing excess ROS. In conclusion, koumine could inhibit the proliferation of HCC cells and promote apoptosis in HCC cells; NF-κB and ERK/p38 MAPK pathways could contribute to koumine functions in a ROS-dependent manner. MDPI 2019-10-02 /pmc/articles/PMC6843837/ /pubmed/31581704 http://dx.doi.org/10.3390/biom9100559 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yuan, Zhihang
Liang, Zengenni
Yi, Jine
Chen, Xiaojun
Li, Rongfang
Wu, Jing
Sun, Zhiliang
Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling
title Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling
title_full Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling
title_fullStr Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling
title_full_unstemmed Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling
title_short Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling
title_sort koumine promotes ros production to suppress hepatocellular carcinoma cell proliferation via nf-κb and erk/p38 mapk signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843837/
https://www.ncbi.nlm.nih.gov/pubmed/31581704
http://dx.doi.org/10.3390/biom9100559
work_keys_str_mv AT yuanzhihang kouminepromotesrosproductiontosuppresshepatocellularcarcinomacellproliferationvianfkbanderkp38mapksignaling
AT liangzengenni kouminepromotesrosproductiontosuppresshepatocellularcarcinomacellproliferationvianfkbanderkp38mapksignaling
AT yijine kouminepromotesrosproductiontosuppresshepatocellularcarcinomacellproliferationvianfkbanderkp38mapksignaling
AT chenxiaojun kouminepromotesrosproductiontosuppresshepatocellularcarcinomacellproliferationvianfkbanderkp38mapksignaling
AT lirongfang kouminepromotesrosproductiontosuppresshepatocellularcarcinomacellproliferationvianfkbanderkp38mapksignaling
AT wujing kouminepromotesrosproductiontosuppresshepatocellularcarcinomacellproliferationvianfkbanderkp38mapksignaling
AT sunzhiliang kouminepromotesrosproductiontosuppresshepatocellularcarcinomacellproliferationvianfkbanderkp38mapksignaling